Publication: P53 protects lung cancer cells against metabolic stress
Submitted Date
2010-06-18
Accepted Date
2010-07-30
Issued Date
2010
Resource Type
Language
eng
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Mahidol University
Bibliographic Citation
International Journal of Oncology. Vol.37, No.6 (2010), 1575-1581
Suggested Citation
Chompunoot Sinthupibulyait, Wanida Ittarat, Clair, William H. St., Clair, Daret K. St. P53 protects lung cancer cells against metabolic stress. International Journal of Oncology. Vol.37, No.6 (2010), 1575-1581. Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/2116
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Title
P53 protects lung cancer cells against metabolic stress
Abstract
Abstract. The preferential use of aerobic glycolysis for energy
production by cancer cells, a phenomenon known as the
‘Warburg effect’, is well recognized and is being considered
for therapeutic applications. However, whether inhibition of
glycolysis will be effective in all types of cancer is unclear.
The current study shows that a glycolytic inhibitor, 2-deoxy-
D-glucose (2DG), exhibits the cytotoxic effect on non-small
cell lung cancer in a p53-dependent manner. 2DG significantly
inhibits ATP production in p53-deficient lung cancer cells
(H358) but not in p53-wt cells (A549). In contrast to p53-wt
cells, p53-defective cells are unable to compensate for their
need of energy via oxidative phosphorylation (OXPHOS)
when glycolysis is inhibited. In the presence of p53, increased
ROS from OXPHOS increases the expression of p53 target
genes known to modulate metabolism, including synthesis of
cytochrome c oxidase 2 (SCO2) and TP53-induced glycolysis
and apoptosis regulator (TIGAR). Importantly, 2DG selectively
induces the expression of the antioxidant enzymes manganese
superoxide dismutase (MnSOD) and glutathione peroxidase 1
(GPx1) in a p53-dependent manner. The results demonstrate
that the killing of cancer cells by the inhibitor of glycolysis is
more efficient in cancer cells without functional p53 and that
p53 protects against metabolic stress by up-regulation of
oxidative phosphorylation and modulation of antioxidants.